Elevated CETP activity improves plasma cholesterol efflux capacity from human macrophages in women.

OBJECTIVE We aim to identify the impact of endogenous cholesteryl ester transfer protein (CETP) activity on plasma capacity to mediate free cholesterol efflux from human macrophages. METHODS AND RESULTS Endogenous plasma CETP activity was measured in a population of 348 women. We defined a low CETP group corresponding to subjects displaying an endogenous plasma CETP activity within the first tertile and a high CETP group corresponding to subjects with an endogenous plasma CETP activity within the third tertile. Subjects from the high CETP activity group displayed a significant increase in the capacity of their plasma (+8.2%; P=0.001) to mediate cholesterol efflux from human acute monocytic leukemia cell line human macrophages and from ATP-binding cassette transporter A1-dependent pathway (+23.4%; P=0.0001) as compared with those from the low CETP activity group. Multivariate analyses revealed that the impact of CETP activity was independent of plasma lipids levels. Pre-β1-high-density lipoprotein concentrations were significantly elevated (+29.6%; P=0.01) in the high CETP activity group as compared with the low CETP activity group. A positive correlation between pre-β1-high-density lipoprotein levels and plasma efflux efficiency from human acute monocytic leukemia cell line human macrophages was observed (r=0.29, P=0.02). CONCLUSIONS CETP leading to the improvement of plasma efflux capacity, as a result of efficient pre-β-high-density lipoprotein formation and ATP-binding cassette transporter A1 efflux, should be preserved to prevent lipid accumulation in human macrophages.